The objective of the proposed work is to define and characterize those surface-associated, or cell-bound, factors which contribute to the virulence of enteropathogenic Escherichia coli, including enterotoxigenic E. coli (ETEC) and the classical enteropathogenic E. coli serogroups (EPEC). The primary event in bacterial secretory diarrhea is attachment of the bacteria to the epithelial cell surface of the intestinal mucosa via specific structures on the surface of the bacteria. These are usually, but not necessarily, in the form of fimbriae, otherwise called pili. Following adhesion, bacterial multiplication results in gross colonization of the mucosal surface with subsequent production of enterotoxic substances. This investigator and coworkers have discovered and partially characterized two major colonization factor antigens of ETEC; these are CFA/I and CFA/II. These studies are being extended to include the EPEC. It has been determined that the CFAs of ETEC are mannose-resistant hemagglutinins (MRHAs) and that enteropathogenic E. coli other than ETEC also produce MRHAs which relate to virulence but these are antigenically different. The mechanism of pathogenesis of EPEC is not understood except that these cause enteritis in infants and young children. Preliminary work by this and other investigators indicates that the mode of pathogenesis is very similar to that of the salmonellae. This is being investigated using adherence tests with mammalian intestinal cells in tissue culture and with the intact infant rabbit.